OBJECTIVE: The main long-term objective of this work is to define the role of gd T lymphocytes in SIV/HIV infections and utilize this information in our AIDS immunotherapy trials. Our 1997 efforts in this area focused on analyzing the reactivities of gd T cells against various nonpeptidic ligands. RESULTS Results from this study suggest that the assessment of Vg9Vd2 responses may be useful for monitoring the efficacy of antimycobacterial therapies. The responsiveness of peripheral blood Vg9Vd2 T cells, which recognize nonpeptidic mycobacterial antigens, was measured in children (1 to 12 years old) with primary Mycobacterium tuberculosis infections. The Vg9Vd2 T-cell responses were highly increased in infected children in comparison with age-matched controls. This augmented Vg9Vd2 T-cell reactivity subsided after successful anti-biotic chemotherapy, suggesting that persistent exposure to mycobacterial antigens is required for the maintenance of gd T-cell activation in vivo. Since the functional activities of rhesus macaque (Macaca mulatta) Vg9Vd2 T cells are very similar to those of Homo sapiens, the in vivo reactivity of Vg9Vd2 T cells to nonpeptidic antigens was further analyzed in a rhesus monkey model system. Intravenous injections of nonpeptidic antigens induced an activated state of simian Vg9Vd2 T cells which decreased after two months, i.e., with a time-course similar to that seen in M. tuberculosis-infected children. Thus it appears that Vg9Vd2 T cells are activated in vivo during the primary M. tuberculosis infection and the persistence of this activation state depends on the exposure to nonpeptidic antigens. FUTURE DIRECTIONS In 1998, we plan to develop methods for in vivo modulations of gd T-cell activities using vaccinations with nonpeptidic antigens. KEY WORDS nonpeptidic antigens, gd T cells